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We studied the effect of allopregnanolone on stress-induced anxiety caused by intranasal administration of corticoliberin to male Wistar rats. Active and passive rats were selected by their T-maze behavior and then were tested in elevated plus maze for initial anxiety level. Basing on test results, the animals were divided into following groups: active high-anxiety rats, active low-anxiety rats, and passive animals. Rats of the experimental subgroups received subcutaneous injection of allopregnanolone (0.2 mg/kg body weight), control animals received saline. In 30 min, all animals intranasally received corticoliberin (0.5 μg into each nostril) and then were tested in elevated plus maze. Passive animals demonstrated increased anxiety after corticoliberin administration against the background of allopregnanolone. Under the same conditions, low-anxiety rats demonstrated reduced anxiety, while in active high-anxiety animals, only an increase of motor activity was observed. Hence, the effect of allopregnanolone on anxiety level under stress conditions depends on individual typologic features of animal behavior.

Corticoliberin (corticotrophin-releasing factor, CRF, CRH) is an active regulator of endocrine, autonomic, and immune functions in stress, as well as a mediator of anxiety, determining the behavioral stress response. The present report describes studies of its action on neuron activity evoked by microstimulation of olfactory cortex slices. Behavioral testing in a T maze was used to select individuals with a passive behavioral strategy from a population of Wistar rats, and the animals were subjected to water immersion. Olfactory cortex slices were prepared 10 days later and evoked focal potentials were recorded on perfusion with medium containing corticoliberin (0.1 microM). Among active rats, 60% of slices retained high excitability after stress, and corticoliberin produced only insignificant reductions in the amplitudes of excitatory potentials in these slices, simultaneously increasing the amplitudes of inhibitory potentials. Low excitability was found in 40% of slices from active stressed rats, and corticoliberin had a significant inhibitory effect in these slices. Addition of corticoliberin to the incubation medium used for slices from passive rats with initially low excitability led to complete blockade of synaptic transmission. These data support the involvement of corticoliberin in the development of depression.

The behavior of rats in a T-maze was used to select individuals with a passive strategy of adaptive behavior from a population of Wistar rats. These animals were subjected to water immersion and olfactory cortex slices were prepared from the brain 10 days later and used for recording of evoked focal potentials and the effects of tetanic stimulation. Postsynaptic potentials, of both the AMPA and NMDA types, were initially of decreased amplitude in passive rats. After unavoidable stress, the suppression of excitatory potentials increased and there was a simultaneous increase in the amplitude of inhibitory GABAB-ergic mechanisms. Addition of corticoliberin (10(-10) M) to the incubation medium led to reversible blockade of synaptic transmission. Tetanic stimulation of slices from stressed rats led to the development of posttetanic depression in 84% of cases and to post-tetanic potentiation in 12%; this is evidence for profound changes in synaptic transmission. Thus, activation of corticoliberinergic mechanisms in cortical structures does not promote recovery from depressive states in rats with the passive behavioral strategy induced by unavoidable stress.

Experiments were performed on male Wistar rats. The specimens with an active strategy of behavior were exposed to unavoidable water-immersion stress. Surviving slices of the olfactory cortex were obtained 10 days after stress. The neurohormone had a strong inhibitory effect in 40% slices from active rats. The activity of glutamate receptors decreased, while the function of GABA receptors increased in 60% slices. Our results indicate that the depressive state of behaviorally active animals due to exposure to unavoidable stress is not necessarily mediated by the corticoliberinergic mechanisms in cortical structures.

Active and passive Wistar rats were subjected to single water immersions, after which they showed signs of post-stress depression. Administration on this background of the peptide CRH-R1 receptor blocker astressin prevented the development of behavioral deficit in active individuals but had no effect on the behavior of passive rats. These results lead to the conclusion that corticoliberin receptor blockers are effective in the treatment of post-stress depression only for individuals with an initially active behavioral strategy.

Animals with active and passive strategies of adaptive behavior were selected from a population of Wistar rats by testing in a T maze to measure the indexes of behavioral passivity and behavioral activity. After single (stress) or two (stress-restress) water immersions, individual changes in adaptive behavior were used to study the development of post-stress psychopathology and its interaction with the initial behavioral strategy. In the unavoidable aversive environment, active and passive rats developed different types of post-stress depression, only passive individuals fulfilling the criteria of post-traumatic stress disorder.